Antidepressant exposure GWAS multi-ancestry meta-analysis

library(dplyr)

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library(tidyr)
library(readr)
library(stringr)
library(ggplot2)
library(ggrepel)
library(topr)
library(UpSetR)
library(plyranges)

## Loading required package: BiocGenerics

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## Loading required package: IRanges

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library(ieugwasr)

## OpenGWAS updates:

##   Date: 2024-05-17

##   [>] OpenGWAS is growing!

##   [>] Please take 2 minutes to give us feedback -

##   [>] It will help directly shape our emerging roadmap

##   [>] https://forms.office.com/e/eSr7EFAfCG

library(gwascat)

## gwascat loaded.  Use makeCurrentGwascat() to extract current image.

##  from EBI.  The data folder of this package has some legacy extracts.

# Source helper functions 
source("multi_funcs.R")

Principal components

plot_ancestry_PCs("antidep-2501-mrmega-N06A.log")

plot_ancestry_PCs("antidep-2501-mrmega-N06AA.log")

plot_ancestry_PCs("antidep-2501-mrmega-N06AB.log")

Manhattan plots

mrmega_n06a <- get_sumstats("antidep-2501-mrmega-N06A-DIV.gz")

## Rows: 10650849 Columns: 29
## ── Column specification ────────────────────────────────────────────────────────
## Delimiter: "\t"
## chr  (5): MarkerName, EA, NEA, Effects, CHR
## dbl (23): Chromosome, Position, EAF, Nsample, Ncohort, beta_0, se_0, beta_1,...
## lgl  (1): Comments
## 
## ℹ Use `spec()` to retrieve the full column specification for this data.
## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

mrmega_n06aa <- get_sumstats("antidep-2501-mrmega-N06AA-DIV.gz")

## Rows: 9007284 Columns: 29
## ── Column specification ────────────────────────────────────────────────────────
## Delimiter: "\t"
## chr  (5): MarkerName, EA, NEA, Effects, CHR
## dbl (23): Chromosome, Position, EAF, Nsample, Ncohort, beta_0, se_0, beta_1,...
## lgl  (1): Comments
## 
## ℹ Use `spec()` to retrieve the full column specification for this data.
## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

mrmega_n06ab <- get_sumstats("antidep-2501-mrmega-N06AB-DIV.gz")

## Rows: 10033491 Columns: 29
## ── Column specification ────────────────────────────────────────────────────────
## Delimiter: "\t"
## chr  (5): MarkerName, EA, NEA, Effects, CHR
## dbl (23): Chromosome, Position, EAF, Nsample, Ncohort, beta_0, se_0, beta_1,...
## lgl  (1): Comments
## 
## ℹ Use `spec()` to retrieve the full column specification for this data.
## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

mrmega_n06a_assoc <- get_assoc(mrmega_n06a, "N06A")
mrmega_n06aa_assoc <- get_assoc(mrmega_n06aa, "N06AA")
mrmega_n06ab_assoc <- get_assoc(mrmega_n06ab, "N06AB")

plot_manhat(mrmega_n06a_assoc)

plot_manhat(mrmega_n06aa_assoc)

plot_manhat(mrmega_n06ab_assoc)

Clumps

clumps_N06A <- get_clumps("antidep-2501-mrmega-N06A-DIV.clumps.tsv")

## Rows: 26 Columns: 32
## ── Column specification ────────────────────────────────────────────────────────
## Delimiter: "\t"
## chr  (5): MarkerName, EA, NEA, Effects, CHR
## dbl (26): Locus, Chromosome, Position, EAF, Nsample, Ncohort, beta_0, se_0, ...
## lgl  (1): Comments
## 
## ℹ Use `spec()` to retrieve the full column specification for this data.
## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

clumps_N06AA <- get_clumps("antidep-2501-mrmega-N06AA-DIV.clumps.tsv")

## Rows: 2 Columns: 32
## ── Column specification ────────────────────────────────────────────────────────
## Delimiter: "\t"
## chr  (4): MarkerName, EA, NEA, Effects
## dbl (27): Locus, Chromosome, Position, EAF, Nsample, Ncohort, beta_0, se_0, ...
## lgl  (1): Comments
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## ℹ Use `spec()` to retrieve the full column specification for this data.
## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

clumps_N06AB <- get_clumps("antidep-2501-mrmega-N06AB-DIV.clumps.tsv")

## Rows: 6 Columns: 32
## ── Column specification ────────────────────────────────────────────────────────
## Delimiter: "\t"
## chr  (5): MarkerName, EA, NEA, Effects, CHR
## dbl (26): Locus, Chromosome, Position, EAF, Nsample, Ncohort, beta_0, se_0, ...
## lgl  (1): Comments
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## ℹ Use `spec()` to retrieve the full column specification for this data.
## ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

clumps_N06A

clumps_N06AA

clumps_N06AB

Catalogue

gwcat <- get_cached_gwascat()

gwascat_N06A_table <- look_up_snps(clumps_N06A, gwcat)
gwascat_N06AA_table <- look_up_snps(clumps_N06AA, gwcat)
gwascat_N06AB_table <- look_up_snps(clumps_N06AB, gwcat)

write.csv(gwascat_N06A_table, "multi_files/gwas_cat_N06A_table.csv", quote = F, row.names = F)
write.csv(gwascat_N06AA_table, "multi_files/gwas_cat_N06AA_table.csv", quote = F, row.names = F)
write.csv(gwascat_N06AB_table, "multi_files/gwas_cat_N06AB_table.csv", quote = F, row.names = F)